Dataset Information

Impact of a blood-stage vaccine on Plasmodium vivax malaria.

ABSTRACT:

Background

There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside of Africa.

Methods

We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of P. vivax Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months). Delayed regimens were due to trial halts during the COVID-19 pandemic. Volunteers underwent heterologous controlled human malaria infection (CHMI) with blood-stage P. vivax parasites at 2-4 weeks following their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparison of parasite multiplication rate (PMR) in blood post-CHMI, modelled from parasitemia measured by quantitative polymerase-chain-reaction (qPCR).

Results

Thirty-two volunteers were enrolled and vaccinated (n=16 for each vaccine). No safety concerns were identified. PvDBPII/Matrix-M™, given in the delayed dosing regimen, elicited the highest antibody responses and reduced the mean PMR following CHMI by 51% (range 36-66%; n=6) compared to unvaccinated controls (n=13). No other vaccine or regimen impacted parasite growth. In vivo growth inhibition of blood-stage P. vivax correlated with functional antibody readouts of vaccine immunogenicity.

Conclusions

Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431 .

SUBMITTER: Hou MM

PROVIDER: S-EPMC9164524 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Impact of a blood-stage vaccine on <i>Plasmodium vivax</i> malaria.

Hou Mimi M MM Barrett Jordan R JR Themistocleous Yrene Y Rawlinson Thomas A TA Diouf Ababacar A Martinez Francisco J FJ Nielsen Carolyn M CM Lias Amelia M AM King Lloyd D W LDW Edwards Nick J NJ Greenwood Nicola M NM Kingham Lucy L Poulton Ian D ID Khozoee Baktash B Goh Cyndi C Mac Lochlainn Dylan J DJ Salkeld Jo J Guilotte-Blisnick Micheline M Huon Christèle C Mohring Franziska F Reimer Jenny M JM Chauhan Virander S VS Mukherjee Paushali P Biswas Sumi S Taylor Iona J IJ Lawrie Alison M AM Cho Jee-Sun JS Nugent Fay L FL Long Carole A CA Moon Robert W RW Miura Kazutoyo K Silk Sarah E SE Chitnis Chetan E CE Minassian Angela M AM Draper Simon J SJ

medRxiv : the preprint server for health sciences 20220530

<h4>Background</h4>There are no licensed vaccines against <i>Plasmodium vivax</i> , the most common cause of malaria outside of Africa.<h4>Methods</h4>We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of <i>P. vivax</i> Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvan ...[more]

PMID: 35664997

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